Polylactic acid is one of biodegradable polymers, and has been applied to drug carriers in various forms because it has excellent biocompatibility and it is hydrolyzed into lactic acid non-harmful to the human body. Polylactic acid derivatives including a polylactic acid have various properties depending on molecular weight. For example, a polylactic acid derivative having a molecular weight of 2000 daltons or higher is not soluble in water, and thus has been developed into microspheres, nanoparticles, polymeric gels and implant agents.
In addition, polylactic acid derivatives used as drug carriers may be modified in terms of molecular weight and copolymer constitution to control drug release rate. In controlling drug release rate, purity of a polylactic acid derivative plays an important role. During the polymerization of a polymer from monomers, unreacted monomers may remain in the polymer to decrease the purity of the polylactic acid derivative. If the content of unreacted monomers is high, the polylactic acid derivative has a broad molecular weight distribution. As a result, administration of a low-molecular weight polymer molecule into the human body may cause excessive drug release at the initial time. Moreover, while the remaining monomers are decomposed, pH decreases and the polymer decomposition rate increases. This makes it difficult to accomplish prolonged drug release.
According to the related art, a polylactic acid is purified by a solvent/non-solvent method. The method is advantageous in that a solidified polymer may be obtained, when the polymer has a high molecular weight or when preparing an L,L-polylactic acid derivative. However, when the polymer has a low molecular weight or when preparing non-crystalline D,L-polylactic acid derivatives, gel-like precipitate is generated upon settling in a non-solvent, making it difficult to purify the polymer.
Particularly, in the case of D,L-polylactic acid with a low molecular weight, precipitation of its acetone solution in distilled water causes generation of gel-like precipitate. Such gel-like precipitate hardly allows moisture removal even when subjected to vacuum drying. Thus, removing moisture needs a long time. In addition, under the high-temperature vacuum condition, condensation polymerization may occur, making it difficult to control the molecular weight. Further, under the same condition, lactide monomers may be produced.
Additionally, when the polymer has a high molecular weight or when preparing crystalline L,L-polylactic acid, solidified polylactic acid may be obtained through the above-mentioned solvent/non-solvent method. However, during the purification based on the solvent/non-solvent method, the monomers and an organometal catalyst may co-precipitate in the non-solvent and be not removed effectively therefrom.
Meanwhile, a method for purifying D,L-polylactic acid with a low molecular weight by liquid-liquid phase separation is also known. After the polymerization, the polymer is dissolved in methanol or ethanol under heating. Then, the polymer solution is refrigerated at a temperature of −78° C. so that phase separation occurs. Polylactic acid with a low molecular weight is dissolved in the upper organic solvent layer, while polylactic acid with a high molecular weight is solidified in the lower layer. The lower layer is separated and the solvent is distilled off to remove the monomers and oligomers. In this manner, highly purified D,L-polylactic acid having a narrow molecular weight distribution is provided. However, the lactide monomers produced during the polymerization is dissolved in an alcohol solvent at high temperature but recrystallized therein at low temperature. Therefore, the monomers are not removed effectively from D,L-polylactic acid even after carrying out the above method.